The Association of Cholesterol Uptake and Synthesis with Histology and Genotype in Cortisol-Producing Adenoma (CPA).

Cortisol-producing adenoma (CPA) is composed of clear and compact cells. Clear cells are lipid abundant, and compact ones lipid poor but associated with higher production of steroid hormones. PRKACA mutation (PRKACA mt) in CPA patients was reported to be associated with more pronounced clinical manifestation of Cushing's syndrome. In this study, we examined the association of histological features and genotypes with cholesterol uptake receptors and synthetic enzymes in 40 CPA cases, and with the quantitative results obtained by gas chromatography-mass spectrometry (GC-MS) analysis in 33 cases to explore their biological and clinical significance. Both cholesterol uptake receptors and synthetic enzymes were more abundant in compact cells. GC-MS analysis demonstrated that the percentage of compact cells was inversely correlated with the concentrations of cholesterol and cholesterol esters, and positively with the activity of cholesterol biosynthesis from cholesterol esters. In addition, hormone-sensitive lipase (HSL), which catalyzes cholesterol biosynthesis from cholesterol esters, tended to be more abundant in compact cells of PRKACA mt CPAs. These results demonstrated that both cholesterol uptake and biosynthesis were more pronounced in compact cells in CPA. In addition, more pronounced HSL expression in compact cells of PRKACA mt CPA could contribute to their more pronounced clinical manifestation.

Method for the Large-Scale Synthesis of Multifunctional 1,4-Dihydro-pyrrolo[3,2-b]pyrroles.

A thorough investigation has enabled the optimization of the synthesis of 1,4-dihydro-pyrrolo[3,2-b]pyrroles. Although salts of such metals as vanadium, niobium, cerium, and manganese were found to facilitate the formation of 1,4-dihydro-pyrrolo[3,2-b]pyrroles from amines, aldehydes, and diacetyl, we confirmed that iron salts are the most efficient catalysts. The conditions identified (first step: toluene/AcOH = 1:1, 1 h, 50 °C; second step: toluene/AcOH = 1:1, Fe(ClO4)3·H2O, 16 h, 50 °C) resulted in the formation of tetraarylpyrrolo[3,2-b]pyrroles in a 6-69% yield. For the first time, very electron-rich substituents (4-Me2NC6H4, 3-(OH)C6H4, pyrrol-2-yl) originating from aldehydes and sterically hindered substituents (2-ClC6H4, 2-BrC6H4, 2-CNC6H4, 2-(CO2Me)C6H4, 2-(TMS-C≡C)C6H4) present on anilines can be appended to the pyrrolo[3,2-b]pyrrole core. It is now also possible to prepare 1,4-dihydropyrrolo[3,2-b]pyrroles bearing an ordered arrangement of N-substituents and C-substituents ranging from coumarin, quinoline, phthalimide to truxene. These advances in scope enable independent regulations of many desired photophysical properties, including the Stokes shift value and emission color ranging from violet-blue through deep blue, green, yellow to red. Simultaneously, the optimized conditions have finally allowed the synthesis of these extremely promising heterocycles in amounts of more than 10 g per run without a concomitant decrease in yield or product contamination. Empowered with better functional group compatibility, novel derivatization strategies were developed.

Comparison of foot pressure distribution and foot kinematics in undulatory underwater swimming between performance levels.

This study aimed to elucidate the foot kinematics and foot pressure difference characteristics of faster swimmers in undulatory underwater swimming (UUS). In total, eight faster and eight slower swimmers performed UUS in a water flume at a flow velocity set at 80% of the maximal effort swimming velocity. The toe velocity and foot angle of attack were measured using a motion capture system. A total of eight small pressure sensors were attached to the surface of the left foot to calculate the pressure difference between the plantar and dorsal sides of the foot. Differences in the mean values of each variable between the groups were analysed. Compared to the slower swimmers, the faster swimmers exhibited a significantly higher swimming velocity (1.53 ± 0.06 m/s vs. 1.31 ± 0.08 m/s) and a larger mean pressure difference in the phase from the start of the up-kick until the toe moved forward relative to the body (3.88 ± 0.65 kPa vs. 2.66 ± 1.19 kPa). The faster group showed higher toe vertical velocity and toe direction of movement, switching from lateral to medial at the time of generating the larger foot pressure difference in the up-kick, providing insight into the reasons behind the foot kinematics of high UUS performance swimmers.

Role of Halobenzene Guest Molecules in Modulating Room Temperature Phosphorescence of Benzophenone-Naphthalene Diimide Inclusion Crystals.

Materials exhibiting room temperature phosphorescence (RTP) have recently emerged as a subject of significant interest. In this study, we successfully created inclusion crystals by introducing halobenzenes as guests into a host molecule combining benzophenone with naphthalene diimide. This approach led to the creation of fascinating fluorescence and RTP properties dependent on the guest molecules. Notably, crystals containing chlorobenzene showed cyan fluorescence, while those with iodobenzene displayed red RTP. This difference highlights the impact of the guest molecule on the luminescent properties, with the significant external heavy-atom effect of iodobenzene playing a key role in promoting efficient intersystem crossing between the excited singlet and triplet states. Crystals with bromobenzene exhibited a unique blend of fluorescence and RTP, both from benzophenone and naphthalene diimide, highlighting the moderate heavy-atom effect. These findings reveal composite materials with remarkably diverse and interesting optical characteristics.

How do swimmers control their front crawl swimming velocity? Current knowledge and gaps from hydrodynamic perspectives.

The aim of this study was to review the literature on front crawl swimming biomechanics, focusing on propulsive and resistive forces at different swimming velocities. Recent studies show that the resistive force increases in proportion to the cube of the velocity, which implies that a proficient technique to miminise the resistive (and maximise the propulsive) force is particularly important in sprinters. To increase the velocity in races, swimmers increase their stroke frequency. However, experimental and simulation studies have revealed that there is a maximum frequency beyond which swimmers cannot further increase swimming velocity due to a change in the angle of attack of the hand that reduces its propulsive force. While the results of experimental and simulation studies are consistent regarding the effect of the arm actions on propulsion, the findings of investigations into the effect of the kicking motion are conflicting. Some studies have indicated a positive effect of kicking on propulsion at high swimming velocities while the others have yielded the opposite result. Therefore, this review contributes to knowledge of how the upper-limb propulsion can be optimised and indicates a need for further investigation to understand how the kicking action can be optimised in front crawl swimming.Abbreviations: C: Energy cost [kJ/m]; E: Metabolic power [W, kJ/s]; Fhand: Fluid resultant force exerted by the hand [N]; Ftotal: Total resultant force [N] (See Appendix A); Fnormal: The sum of the fluid forces acting on body segments toward directions perpendicular to the segmental long axis, which is proportional to the square of the segmental velocity. [N] (See Appendix A); Ftangent: The sum of the fluid forces acting on body segments along the direction parallel to the segmental long axis, which is proportional to the square of the segmental velocity. [N] (See Appendix A); Faddmass: The sum of the inertial force acting on the body segments due to the acceleration of a mass of water [N] (See Appendix A); Fbuoyant: The sum of the buoyant forces acting on the body segments [N] (See Appendix A); D: Fluid resistive force acting on a swimmer's body (active drag) [N]; T: Thrust (propulsive) force acting in the swimming direction in reaction to the swimmer's actions [N]; Thand: Thrust force produced in reaction to the actions of the hand [N]; Tupper_limb: Thrust force produced in reaction to the actions of the upper limbs [N]; Tlower_limb: Thrust force produced in reaction to the actions of the lower limbs [N]; Mbody: Whole-body mass of the swimmer [kg]; SF: Stroke frequency (stroke number per second) [Hz]; SL: Stroke length (distance travelled per stroke) [m]; v: Instantaneous centre of mass velocity of the swimmer [m/s]; V-: Mean of the instantaneous centre of mass velocities in the swimming direction over the period of the stroke cycle [m/s]; a: Centre of mass acceleration of the swimmer [m/s2]; V-hand: Mean of the instantaneous magnitudes of hand velocity over a period of time [m/s]; Wtot: Total mechanical power [W]; Wext: External mechanical power [W]; Wd: Drag power (mechanical power needed to overcome drag) [W, Nm/s]; α: Angle of attack of the palm plane with respect to the velocity vector of the hand [deg]; ηo: Overall efficiency [%]; ηp: Propelling efficiency [%]; MAD-system: Measuring Active Drag system; MRT method: Measuring Residual Thrust method.

Relationship Between Hand Kinematics, Hand Hydrodynamic Pressure Distribution and Hand Propulsive Force in Sprint Front Crawl Swimming.

PURPOSE: This study investigated the relationship between hand kinematics, hand hydrodynamic pressure distribution and hand propulsive force when swimming the front crawl with maximum effort. METHODS: Twenty-four male swimmers participated in the study, and the competition levels ranged from regional to national finals. The trials consisted of three 20 m front crawl swims with apnea and maximal effort, one of which was selected for analysis. Six small pressure sensors were attached to each hand to measure the hydrodynamic pressure distribution in the hands, 15 motion capture cameras were placed in the water to obtain the actual coordinates of the hands. RESULTS: Mean swimming velocity was positively correlated with hand speed (r = 0.881), propulsive force (r = 0.751) and pressure force (r = 0.687). Pressure on the dorsum of the hand showed very high and high negative correlations with hand speed (r = -0.720), propulsive force (r = -0.656) and mean swimming velocity (r = -0.676). On the contrary, palm pressure did not correlate with hand speed and mean swimming velocity. Still, it showed positive correlations with propulsive force (r = 0.512), pressure force (r = 0.736) and angle of attack (r = 0.471). Comparing the absolute values of the mean pressure on the palm and the dorsum of the hand, the mean pressure on the dorsum was significantly higher and had a larger effect size (d = 3.71). CONCLUSION: It is suggested that higher hand speed resulted in a more significant decrease in dorsum pressure (absolute value greater than palm pressure), increasing the hand propulsive force and improving mean swimming velocity.

Hydrogen Bond Engineering Visualized by Picometer-Level Distortion of Planar Porphyrin Isomers.

Directly investigating hydrogen bond (HB) dynamics in molecular materials is a challenging task. Here, we report a set of porphyrin isomers, porphycenes, that visualize slight changes on the order of picometers in the intramolecular HB dynamics. Intramolecular HBs of porphycenes were regulated by the systematic modification at meso positions with methyl (Me), cyclopentyl (Cy5), and cyclohexyl (Cy6) moieties. Notably, the quantum yields varied from 35 to 0.04% in chloroform, depending on a slight distortion in the porphycene framework. SC-XRD, XPS, and NMR clearly revealed that the Me and Cy6 moieties increased the nonradiative deactivation by strengthening the intramolecular NH···N HBs whereas Cy5 retained their photoluminescence properties. This is the first example of how the distortion of planar porphyrinoids at the picometer level along with the strength of the intramolecular NH···N HBs can drastically affect their optical properties. The results revealed new avenues of HB engineering based on porphyrinoids.

Effects of exceeding stroke frequency of maximal effort on hand kinematics and hand propulsive force in front crawl.

This study aimed to assess kinematic and kinetic changes in front crawl with various stroke frequency (SF) conditions to investigate why swimming velocity (SV) does not increase above a certain SF (SFmax). Eight male swimmers performed 20 m front crawl four times. The first trial involved maximal effort, whereas SF was controlled during the next three trials. The instructed SFs were 100 (T100%), 110 (T110%), and 120% (T120%) of the SFmax. Through pressure measurement and underwater motion analysis, hand propulsive force (calculated by the difference between the palm and dorsal pressure value and the hand area) and the angle of attack of the hand were quantified, and differences between trials were assessed by a repeated-measures ANOVA. There was no difference in SV between the conditions, while the angle of attack during the latter half of the underwater stroke at T120% was smaller by 25.7% compared with T100% (p = 0.007). The lower angle of attack induced a lower pressure value on the palm that consequently caused a smaller hand propulsive force at T120% than T100% (p = 0.026). Therefore, the decrease in the angle of attack must be minimised to maintain the hand propulsive force.

Highly malleable haem-binding site of the haemoprotein HasA permits stable accommodation of bulky tetraphenylporphycenes.

Iron(iii)- and cobalt(iii)-9,10,19,20-tetraphenylporphycenes, which possess bulky phenyl groups at the four meso positions of porphycene, were successfully incorporated into the haem acquisition protein HasA secreted by Pseudomonas aeruginosa. Crystal structure analysis revealed that loops surrounding the haem-binding site are highly flexible, remodelling themselves to accommodate bulky metal complexes with significantly different structures from the native haem cofactor.

Gram-scale synthesis of porphycenes through acid-catalyzed oxidative macrocyclizations of E/Z-mixed 5,6-diaryldipyrroethenes.

The gram-scale production of porphycene derivatives is reported. This has been achieved by acid-catalyzed ring closure of an E/Z-mixture of 5,6-diaryldipyrroethenes, resulting in the formation of meso-tetraarylporphycenes in yields of up to 80%. E/Z-isomerization of the 5,6-diaryldipyrroethenes under acidic conditions was key to proceed the effective macrocyclization.

The first synthesis of meso-dicycloalkylporphycenes: ring strain effects on structural and optical properties of isomeric porphyrins.

Two novel meso-dicycloalkylporphycenes, namely meso-dicyclopentyl- (Cy5Pc) and meso-dicyclohexylporphycenes (Cy6Pc) are synthesized for the first time in porphycene chemistry. We use intermolecular oxidative coupling of 5,6-dicycloalkydipyrroethenes mediated by hypervalent iodine(iii) reagents. The solution fluorescence maxima of Cy5Pc are more than 400 times as intense as that of Cy6Pc. The results suggested that photoluminescence switching is achieved through the ring strain perturbation of the meso-substituted cycloalkyl groups on the porphycene cavity.